Replacement of nitrite in meat products by natural bioactive compounds results in reduced exposure to N-nitroso compounds: the PHYTOME project
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PROVIDER: PRJNA622780 | ENA |
REPOSITORIES: ENA
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Project description:It has been proposed that endogenously formed N-nitroso compounds (NOCs) are partly responsible for the link between red meat consumption and colorectal cancer (CRC) risk. As nitrite has been indicated as one of the critical factors in the formation of endogenous NOCs, it is of high importance to replace or reduce the nitrite levels in meat. Therefore, the PHYTOME project was initiated (Phytochemicals to reduce nitrite in meat products; www.phytome.eu), an EU funded research project aiming to develop innovative meat products in which the food additive sodium nitrite (E251) has been replaced by natural compounds originating from fruits and vegetables. A human dietary intervention study was conducted in which healthy subjects consumed 300 grams of meat for two weeks, in subsequent order: normal processed red meat, white meat, and red processed meat with standard or reduced levels of nitrite and added phytochemicals. Consumption of standard-nitrite PHYTOME meat products leads to a significant reduction in Apparent Total N-nitroso Compounds (ATNC) levels in faecal water, a surrogate marker of endogenously formed NOCs, as compared to the consumption of conventional processed red meat products. A reduction of nitrite in the PHYTOME meat lowered these levels even further. In addition, DNA strand breaks induced in ex-vivo faecal water exposed Caco-2 cells and O6-methyl-guanine adducts levels in colonic DNA were significantly higher after consumption of normal processed red meat as compared to white meat intake. PHYTOME meat intake resulted in reduced levels of these genotoxic markers, however, these were not statistically significant. Whole genome gene expression analyses in colonic tissue identified differentially expressed genes and genes associated with ATNC, which are related to molecular pathways which may explain cancer risk initiation after intake of processed red meat and cancer risk prevention after intake of the PHYTOME meat. Together these results indicate that addition of natural extracts to conventional processed red meat products results in reduced endogenous formation of NOCs, and may therefore contribute to a reduced risk of CRC, which is mechanistically supported by gene expression analyses.
2021-08-17 | GSE147996 | GEO
Project description:ScopeIt has been proposed that endogenously form N-nitroso compounds (NOCs) are partly responsible for the link between red meat consumption and colorectal cancer (CRC) risk. As nitrite has been indicated as critical factor in the formation of NOCs, the impact of replacing the additive sodium nitrite (E250) by botanical extracts in the PHYTOME project is evaluated.Method and resultsA human dietary intervention study is conducted in which healthy subjects consume 300 g of meat for 2 weeks, in subsequent order: conventional processed red meat, white meat, and processed red meat with standard or reduced levels of nitrite and added phytochemicals. Consumption of red meat products enriched with phytochemicals leads to a significant reduction in the faecal excretion of NOCs, as compared to traditionally processed red meat products. Gene expression changes identify cell proliferation as main affects molecular mechanism. High nitrate levels in drinking water in combination with processed red meat intake further stimulates NOC formation, an effect that could be mitigated by replacement of E250 by natural plant extracts.ConclusionThese findings suggest that addition of natural extracts to conventionally processed red meat products may help to reduce CRC risk, which is mechanistically support by gene expression analyses.
| S-EPMC8530897 | biostudies-literature
Project description:Staphylococcus xylosus is one of the major starter cultures used for meat fermentation because of its crucial role in the reduction of nitrate to nitrite, which contributes to color and flavor development. Despite the long use of these additives, their impact on the physiology of S. xylosus has not yet been explored. We present the first in situ global gene expression profile of S. xylosus in meat supplemented with nitrate and nitrite. More than 600 genes of S. xylosus were differentially expressed at 24 or 72 hours of incubation. They represent more than 20% of the total genes and led us to suppose that addition of nitrate and nitrite to meat leads to a global change in gene expression. This profile revealed that S. xylosus is subject to nitrosative stress caused by reactive nitrogen species generated from nitrate and nitrite. To overcome this stress, S. xylosus has developed several oxidative stress resistance mechanisms, such as modulation of the expression of several genes involved in iron homeostasis and in antioxidant defense. Most of these genes belong to the Fur and PerR regulons respectively. S. xylosus has also counteracted this stress by developing DNA and protein repair. Furthermore, it has adapted its metabolic responseM-bM-^@M-^Tcarbon and nitrogen metabolism, energy production and cell wall biogenesisM-bM-^@M-^Tto the alterations produced by nitrosative stress. Microarray was used to evaluate modification in the transcriptome of S. xylosus C2a strain in the presence (N) or absence (V) of nitroso compounds. Three biological replicates collected on separate days for each meat matrix and labelled following a dye-switch design; for each condition one labeling in Cy3 and one in Cy5.
2014-10-08 | E-GEOD-61514 | biostudies-arrayexpress
Project description:Bioactive Compounds from Endophytic fungus Curvularia sorghina
| PRJEB25627 | ENA
Project description:Study hypothesis: We hypothesise that both colon inflammation and a diet high in red meat increase the endogenous formation of potentially carcinogenic N-nitroso compounds in the human colon and that these compounds increase the colorectal cancer risk, which could (partially) explain the increased colorectal cancer risk that is associated with inflammatory bowel disease and diets high in red meat.
Inflammatory bowel disease is characterised by a chronic inflammation within the gastrointestinal tract, which, in case of ulcerative colitis, is present in the colon and rectum.
Primary outcome(s): 1. Whole genome gene expression modifications by microarray analysis (4x44K Agilent platform)
2. Apparent total nitroso compounds in faecal matter by thermal energy analysis
3. Faecal water genotoxicity (30 minute exposure to 10% faecal water) by comet assay analysis in the adenocarcinoma cell line Caco-2
All outcomes are measured at baseline and post intervention.
| 2415737 | ecrin-mdr-crc
Project description:We conducted a comprehensive screening of bioactive compounds sourced from natural products, specifically targeting those capable of inducing apoptosis while inhibiting tyrosine kinase activity. Our investigation encompassed a diverse range of compounds, including pure compounds, compound mixtures, and peptides, all evaluated within the A549 cell line. To delve into the underlying molecular mechanisms, we employed phosphoproteomics analysis, which enabled us to comprehensively assess the impact of these bioactive compounds on cellular pathways. Through labeling digested proteins with distinct isobaric tags, we meticulously examined the cellular response to each compound. In our experimental design, we included two established chemical drugs, Afatinib and Osimertinib, serving as positive controls. These drugs, both kinase inhibitors utilized in cancer treatment, operate via distinct mechanisms and target different kinases. By comparing the effects of our test compounds with these controls, we aimed to elucidate their potential therapeutic relevance and mechanisms of action. Among the compounds examined were extracts from Phallus indusiatus and Fomes rimosus (Berk.) Cooke, as well as specific compounds like Chamuangone, Cannabigerol (CBG), Cannabidiol (CBD), and NP1-cyclic peptide
2024-03-13 | PXD050555 | Pride
Project description:Various bioactive food compounds may confer health and longevity benefits, possibly through altering or preserving the human epigenome. While bioactive food compounds are widely being marketed as ‘improving health and longevity’ by counteracting harmful effects of poor nutrition and lifestyle, claimed effects are often not adequately documented. Using the honey bee (Apis mellifera) as a model species, we here employed a multi-step screening approach to investigate seven compounds for effects on lifespan and DNA methylation using ELISA and whole genome bisulfite sequencing (WGBS). A positive longevity effect was detected for valproic acid, isovaleric acid, and cyanocobalamin. For curcumin, we found that lifespan shortening caused by ethanol intake, was restored when curcumin and ethanol were co-administered. Furthermore, we identified region specific DNA methylation changes as a result of ethanol intake. Ethanol specific changes in DNA methylation were fully or partially blocked in honey bees receiving ethanol and curcumin together. Ethanol-affected and curcumin-blocked differentially methylated regions covered genes involved in fertility, temperature regulation and tubulin transport. Our results demonstrate fundamental negative effects of low dose ethanol consumption on lifespan and associated DNA methylation changes and present a proof-of-principle on how longevity and DNA methylation changes can be negated by the bioactive food component curcumin. Our findings provide a fundament for further studies of curcumin in mice and humans and offer an avenue to explore regarding possible prevention of health issues related to alcohol consumption.
2021-09-27 | GSE169362 | GEO
Project description:Exploring the therapeutic effects of bioactive compounds has been traditionally approaching by phenotypic screenings followed by functional validation by in vitro assays. The thermal proteome profiling (TPP) has been successfully applied to study drug targets and off-target. We applied a modified protocol based on TPP to elucidate the mechanism of actions (MOA)s of novel bioactives compounds from marine biodiscovery. We have modified the method to gain the specificity for its application to compounds with limited chemical or structural characterization. Method implementation includes increasing the centrifugation force to precipitate the microsomal fraction previous to the thermal shift assay. The range of temperatures has been reduced to optimize the analysis without compromising resolution. Finally, the mass spectrometry analysis was based on label-free quantitative proteomics. Comparison of the targets among methodologies confirmed that the precipitation of the microsomal membranes before TPP is an essential step to discriminate between true targets from proteins precipitates after subcellular fractionation by centrifugation force. As a probe of concept, a novel marine bioactive compound has been analyzed on the hepatic cell line HepG2. We found that 2 targets proteins, aldehyde dehydrogenase and isocitrate dehydoregenase, can be related with beneficial properties towards obesity and obesity-related comorbidities. Identification of targets is key to decipher the MOAs of bioactive compound, predict the mode of action as well as possible harmful effects.
2019-06-28 | PXD013227 | Pride
Project description:Staphylococcus xylosus is one of the major starter cultures used for meat fermentation because of its crucial role in the reduction of nitrate to nitrite, which contributes to color and flavor development. Despite the long use of these additives, their impact on the physiology of S. xylosus has not yet been explored. We present the first in situ global gene expression profile of S. xylosus in meat supplemented with nitrate and nitrite. More than 600 genes of S. xylosus were differentially expressed at 24 or 72 hours of incubation. They represent more than 20% of the total genes and led us to suppose that addition of nitrate and nitrite to meat leads to a global change in gene expression. This profile revealed that S. xylosus is subject to nitrosative stress caused by reactive nitrogen species generated from nitrate and nitrite. To overcome this stress, S. xylosus has developed several oxidative stress resistance mechanisms, such as modulation of the expression of several genes involved in iron homeostasis and in antioxidant defense. Most of these genes belong to the Fur and PerR regulons respectively. S. xylosus has also counteracted this stress by developing DNA and protein repair. Furthermore, it has adapted its metabolic response—carbon and nitrogen metabolism, energy production and cell wall biogenesis—to the alterations produced by nitrosative stress.
2014-10-08 | GSE61514 | GEO
Project description:Macrobrachium nipponense is one of the commonest species threatened by ambient superfluous nitrite. The mechanism of nitrite stress at the molecular level was studied using de novo RNA-Seq to explore the molecular pathways in M. nipponense exposed to the acute nitrite stress (26.05 mg/L nitrite-N) for 24h and the chronic nitrite stress (6.58 mg/L nitrite-N) for 21d. A total of 175.13 million reads were obtained and assembled into 58,871 unigenes with an average length of 1,028.7 bp and N50 of 1,294bp. 2,824 and 2,610 unigenes in the acute and chronic nitrite stress were significantly differentially expressed respectively. Based on the change in GO analysis and KEGG pathway analysis, pathways both in the acute and chronic nitrite stress were glycosphingolipid biosynthesis - ganglio series, alanine aspartate and glutamate metabolism, biotin metabolism and amino sugar and nucleotide sugar metabolism which revealed the commonly functional pathways in acute and chronic nitrite stress. The markedly altered pathways were divided into four sections of immunity, metabolism, cell and others. Immunity section contained the most pathways among the classifications as phagosome, folate biosynthesis, glycerolipid metabolism, glycine, serine and threonine metabolism, selenoamino acid metabolism, cysteine and methionine metabolism, amino sugar and nucleotide sugar metabolism and taurine and hypotaurine metabolism in the acute nitrite stress and lysosome, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, glycosaminoglycan degradation and amino sugar and nucleotide sugar metabolism in the chronic nitrite stress. This is the first report of whole molecular responses of M. nipponense under acute and chronic nitrite stress through de novo transcriptome sequencing. The findings of this study will further promote the understanding of the underlying molecular mechanisms of the nitrite stress for crustacean species.
2016-11-04 | GSE74684 | GEO